Amides from imino esters

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

Alkylations by oxonium salts have added several new weapons to the synthetic chemist s armamentarium. For example, the O-alkylated products from amides [R1C(OR)=NR2R3]+ (R == CH3 or C2H5) may be hydrolyzed under mild conditions to amines and esters,14-34 reduced to the amines RjCH-jNRaRa by sodium borohydride,13 converted to amide acetals RiC(OR)2NR2R3 by alkoxides,4-16 and (for R3 = H) deproton-ated to the imino esters R1C(OR)=NR2.16-18 Amide acetals and imino esters are themselves in turn useful synthetic intermediates. Indeed, oxonium salts transform the rather intractable amide group into a highly reactive and versatile functionality, a fact elegantly exploited in recent work on the synthesis of corrins.34... 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

The imino group ( = NH), the bivalent ammonia radical, corresponds to bivalent oxygen and compounds result from the replacement of carbonyl oxygen with this imino radical. We have, for example, imino esters and imino acid amides. 

From acid amides, lactamidines and cyclic imino esters 575... 

Not only the Pinner synthesis provides alkoxymethyleneiminium salts the action of chloroformic acid esters on primary or secondary amides or thioamides ° as well as on lactams is a versatile method to get these salts and from them the imino esters, e.g. (230 equation 125). Primary and secondary amides have been alkylated by several reagents and the iminium salts thus formed were converted to imino esters with the aid of bases. A collection of imino esters prepared by this method can be found in a review the more recent results listed in Table 5 demonstrate the scope of this procedure. 

Pinner synthesis of orthoesters starting from alkoxymethyleneiminium salts (410 equation 192) (imino ester hydrohalides) is a standard procedure, which has been reviewed several times.For some more recent results see ref. 7. Closely related to this reaction is the alcoholysis of IV-alkyl- and NJ -di-alkyl-alkoxymethyleneiminium salts or acid amide-acid halide adducts. Orthoesters are formed via N//-dialkylalkoxymethyleneiminium salts when amide acetals (411 Scheme 74) are alcoholyzed in the presence of acetic acid. - ... 

Carboxylic acid amides from nitriles via imino ester hydrochlorides... 

These compounds cannot be made by direct chlorination and thus the process is of practical value. This reaction is well known for noncyclic amides, and it is used to prepare imide chlorides (6.7) and from them imino-esters (6.8). 

Other defects that may occur in polyAN include acrylamide (10) and acrylic acid (11) units, resulting from adventitious hydrolysis of AN units, and also derived cyclic structures such as anhydrides (12), imino-amides (13) and imino-esters (14). These structures give rise to characteristic additional peaks in the and NMR spectra of the polymer and they also contribute to the purely aliphatic regions of the spectra [68-70]. 

Cross-linking prevents denaturation from occurring under the severe conditions of manipulation and keeps the active site region intact. The most used cross-linking agents are imino esters. By reacting with available lysine side chains, amide bonds are eventually formed between two sections of the polypeptide chain. 

A chiral auxiliary must be easily obtained from the chiral carbon pool generally alcohols or amines are used, since they can be readily covalently bound to substrates e.g., carboxylic acids27, ketones or aldehydes in the form of esters, amides, ketals. or imino-derivatives. 

N-t-butyl derivatives (e.g., 58) can give satisfactory results but are prone to a number of side reactions, including that just mentioned.173-175 Diacyl-amides (63) may arise as by-products from the ketoketenimine via an imino-anhydride (as shown in Scheme 11) rather than from the enol ester.176 Tetrahydrobenzisoxazolium ions (59) and related compounds are promising as far as freedom from rearrangement and lack of promotion of racemiza-tion are concerned, but they do not appear to have been evaluated in actual peptide syntheses.171 Although beyond the scope of this review, benzisox-azolium salts have also been applied as reagents for peptide synthesis.177,178... 

Cat heps in C, dipeptidyl transferase, dipeptidyl amino peptidase I. Isoln from beef spleen Tallan el al, J. Biot. Chem. 194, 793 (1952) de la Haba et al, ibid. 234, 316 0 959)-Hydrolyzes dipeptidyl amides or esters bearing a free a-amino (or a-imino) group in the N-terminal position, esp. those containing an aromatic amino acid adjacent to the free a -amino group Planta, Gruber, Biochtm. Biophys. Acta 53, 443 (1961) Wurz et al. Biochemistry 1, 19 (1962). Enhances the proteolysis of prothrombin to thrombin and thus plays an important role in blood dotting Purcell, Barnhart, flio-chim. Biophys. Acta 78, 800 (1963),... 

The chemical study was carried out on rifamycin S, derived from rifamycin B by the series of simple reactions shown earlier in Fig. 3. The key degradation of rifamycin S began with its methylation (Fig. 12) with methyl iodide and silver oxide to yield two isomeric derivatives, the imino methyl ether of the amide function (16) and the 21-O-methyl ether (17). The diacetyl derivative formed from the monomethyl ether (17) showed no infrared — OH bands, indicating a total of three hydroxyl groups for rifamycin S. The imino methyl ether (16), unlike rifamycin S, could be cleaved by mild methanolysis (Fig. 12), which yielded mainly two products, the aromatic naphthoquinone derivative (18), and the aliphatic dimethyl acetal methyl ester (19), which could be interconverted with its enol methyl ether (20). Molecular formulas of (18) and (19) showed that these two compounds contained the entire carbon skeleton of the rifamycin molecule. 

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